伯胺的酰胺通过次卤化物处理（或氧化）经过异氰酸酯中间体生成相应的伯胺的反应。最早期的Hofmann降解是使用KOH水溶液和Br2来实施的。这个条件比较剧烈，后续有许多改进的方法，主要是通过氧化剂和碱来实现的。如Keillor等人1997年报道了用NBS做氧化剂，DBU做碱，甲醇中回流25分钟就得到了甲氧羰基保护的胺（JOC, 1997, 62, 7495-7496）。
反应机理
反应实例
【Arch. Pharmacol Res. 1994, 17, 490–491】
【Tetrahedron Lett. 2001, 42, 1449–1452】
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【Phosphorus, Sulfur Silicon Relat. Elem. 2006, 181, 2505–2517】
【Synthesis 2007, 744–748】
A mixture of indazole (4 g, 0.02 mole) and sodium hydroxide(4 g, 0.1 mole) in 30 ml of icewater containing 1.5 g. (0.02 mole) of chlorinewas stirred at room temperature for 2 hours. Then the reaction was warmed on asteam-bath for 1 hour during which time the solution was effected. The solutionwas extracted four times with 50 ml. of ethyl acetate, and the extracts weredried with anhydrous magnesium sulfate. Ether containing hydrogen chloride wasadded, and the mixture was allowed to stand for several days. The solid wascollected recrystallized from ethyl alcohol to give the target compound (3 g,64% yield)
Reference: JACS, 1958, 965
Sodium hydroxide (3.48 kg, 87.0 mol) was dissolved inwater (22 L), and the solution was cooled to 0°C. Bromine (0.63 L, 11.8 mol)was added over 30 min while the temperature was maintained at 0-10°C. In a secondvessel, (R)-tosylasparagine(2.86 kg, 9.48 mol) was added in portions to a solution of NaOH (0.8 kg, 20.0mol) in water (7.2 L) kept cold at 0-10°C. The solution was cooled to 0°C, andthe sodium hypobromite solution was added over 10 min while maintaining atemperature <10°C.After the addition, the resulting yellow solution was aged for 15 min at 10-15°C, and thenheated to 40°C within 30 min. Heating was suspended and the reactiontemperature was allowed to increase to 50°C over 20 min due to the exothermicreaction. When the internal temperature dropped to 45°C, the reaction solutionwas heated to 70°C over 20 min and kept at 70°C for 10 min. HPLC analysismeasured a 90% solution yield of compound 2.The reaction was cooled to 10-15°C, and with vigorous stirring the pHof the mixture was adjusted to 7 by the addition of concentrated hydrochloricacid (4 L), whereupon the product precipitated. The mixture was stirred for 20min at 15°C, and the product was filtered. The cake was slurry washed with water(2-8 L) and then displacement washed with water (8 L). The product was driedwith a nitrogen stream at 20°C affording (2R)-3-amino tosylaminoalanine(1.67 kg, 70%).
Reference: JOC, 1998, 63, 9533-9534.
p-Methoxybenzamide (76 mg, 0.5 mmol), NBS (90 mg, 0.5mmol), and DBU (230 uL) in methanol (5 mL) were heated at reflux for 15 min, atwhich point more NBS (90 mg, 0.5 mmol) was added. The reaction was allowed tocontinue for another 10 min. Methanol was then removed by rotary evaporation, andthe residue was dissolved in 50 mL of EtOAc. The EtOAc solution was washed with5% HCl and saturated NaHCO3 and was then dried over MgSO4.The product, methyl (p-methoxyphenyl) carbamate, was purified by flash columnchromatography (silica gel, eluant 5% EtOAc in CH2Cl2) togive a white solid (86 mg, 95%),
Reference: JOC, 1997, 62, 7495-7496.
A slurry of N-benzyloxycarbonyl-L-asparagine(140 g, 0.53 mol), ethyl acetate(680 mL), acetonitrile (680 mL), water (340 mL),and Iodobenzene I,I-diacetate (200 g, 0.62 mol) was cooled and stirred at 16°C for 30min. the temperature was allowed to reach to 20°C, and the reaction was stirred until completion (4h).The mixture was cooled to 5°C, and the product was filtered, washed with ethylacetate (100 mL), and dried in vacuo at 50°C to afford the target compound (100 g, 79%)
A 500-mL, round-bottomed flask is equipped with amagnetic stirring bar and covered with aluminum foil. To the flask was added asolution of PhI(OCF3)2 (16.13 g, 37.5 mmol) in 37.5 mL of acetonitrile, and theresulting solution was diluted with 37.5 mL of distilled deionized water.Cyclobutanecarboxamide (2.48 g, 25 mmol) was added; the amide quickly dissolves.Stirring was continued for 4 hr, and the acetonitrile was removed with a rotaryevaporator. The aqueous layer was stirred with 250 mL of diethyl ether; to thestirring mixture was added 50 mL of concd hydrochloric acid. The mixture wastransferred to a separatory funnel and the layers were separated. The aqueouslayer was extracted with ether (2*150 mL). The organic fractions were combinedand extracted with 75 mL of 2 N hydrochloric acid. The aqueous fractions arecombined and concentrated with a rotary evaporator using a vacuum pump. Benzene(50 mL) was added to the residue and the solution was concentrated with therotary evaporator, again using a vacuum pump. Addition of benzene andconcentration was repeated five more times. The crude solid was dried underreduced pressure over sulfuric acid overnight. To the product was added 5 mL ofabsolute ethanol and 35 mL of anhydrous ether, and the solution was heated atreflux on a steam bath. Ethanol was added slowly to the mixture, with swirling,until all the material was dissolved; the solution was cooled to roomtemperature. Anhydrous ether was added slowly until crystallization justbegins. The flask was placed in the freezer and the product was allowed tocrystallize. Filtration of the product and drying overnight under reducedpressure over phosphorus pentoxide to provide cyclobutylamine hydrochloride(1.86–2.06 g, 69–77%).
Reference:Organic Syntheses, Coll. Vol. 8, p.132; Vol. 66, p.132
编译自：Name Reactions （A Collection of Detailed Reaction Mechanisms）, Jie Jack Li, Hofmann rearrangement，page 319-320.